Bone-marrow compartment under chronic γ- irradiation conditions ex vivo

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Abstract

Long-term exposure to ionizing radiation at low doses is one of the risk factors for astronauts’ health, at the same time, hematopoietic disorders caused by damage to bone marrow (BM) cells are the most common result of irradiation. The aim of this work was to evaluate the effects of chronic exposure to ionizing radiation on hematopoietic stem and progenitor cells (HSPCs) and BM stromal progenitor cells. In radiation exposure modeling, rats were exposed to 10-fold external fractionated gamma-irradiation at a total dose of 500 cGy for 33 days. The control group of animals was kept in standard vivarium conditions. The cellular composition and functional characteristics of rat femoral BM-derived cells were examined. A decrease in BM cellularity and changes in the expression of surface markers were observed after irradiation, which may indicate a disruption in the hematopoietic and non-hemopoietic cells communication. Stromal progenitor cells after irradiation were characterized by higher levels of induced and spontaneous adipogenic differentiation and reduced proliferative potential. The number of different hematopoietic colonies, except CFU-GM and the total number of colonies were decreased in the experimental group. After irradiation the culture of BM-derived cells was characterized by a higher production of cytokines, which inhibit HSPC proliferation (IL-18, IFNγ) and activate their differentiation (IL-6). There was also an increase in the expression of pro-resorptive genes and cytokines (Sost) along with a decrease in the expression of genes involved in osteogenesis. Thus, it was demonstrated that chronic fractionated irradiation in the low dose range causes negative changes in the stromal and hematopoietic BM compartment, which may lead to impaired hematopoiesis.

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About the authors

Elena A. Markina

State Scientific Center of the Russian Federation – The Institute of Biomedical Problems of the Russian Academy of Sciences

Email: goncharova-tim@list.ru
ORCID iD: 0000-0003-0631-9082
Russian Federation, Moscow

Polina I. Bobyleva

State Scientific Center of the Russian Federation – The Institute of Biomedical Problems of the Russian Academy of Sciences

Email: blastoblast@gmail.com
ORCID iD: 0000-0002-5904-1654
Russian Federation, Moscow

Olga V. Zhidkova

State Scientific Center of the Russian Federation – The Institute of Biomedical Problems of the Russian Academy of Sciences

Author for correspondence.
Email: flain-fish@yandex.ru
ORCID iD: 0000-0001-6574-827X
Russian Federation, Moscow

Pavel V. Lashukov

State Scientific Center of the Russian Federation – The Institute of Biomedical Problems of the Russian Academy of Sciences

Email: flain-fish@yandex.ru
ORCID iD: 0000-0001-6843-2158
Russian Federation, Moscow

Ludmila B. Buravkova

State Scientific Center of the Russian Federation – The Institute of Biomedical Problems of the Russian Academy of Sciences

Email: buravkova@imbp.ru
ORCID iD: 0000-0001-6994-557X
Russian Federation, Moscow

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2. Fig.1. Hematopoietic colonies formed by bone marrow cells from the femoral bone of Wistar rats. A – colony-forming unit (CFU) of granulocytes and macrophages, B – CFU of macrophages, C – CFU of granulocytes, D – erythrocyte colony-forming unit, E – CFU of B lymphocytes precursors. Dark-field microscopy. Lens: Nikon Plan Flour 4/0/13 ∞/1/2 WD16.5.

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3. Fig. 2. Number of hematopoietic colonies formed by myeloid and lymphoid precursors from rat bone marrow. Total number of colony-forming units (CFU). А – total number of colony-forming units (CFU), B – CFU-G – CFU of granulocytes, C – BFU-E – burst-forming unit-erythroid, D – CFU-preB – CFU of B lymphocytes precursors, E – CFU-GM – colony-forming unit of granulocytes and macrophages, F – CFU-M – CFU of macrophages. C – vivary control, I – irradiation. * Significant difference compared to control values (p < 0.05), n = 3.

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4. Fig. 3. Differential gene expression profile in rat femoral BM-derived cells. Data are presented as a heat map (2-∆∆Ct).

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